Percorrer por autor "Barreira, Maria"
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- Brain-Targeted Delivery of Pre-miR-29b Using Lactoferrin-Stearic Acid-Modified-Chitosan/Polyethyleneimine PolyplexesPublication . Pereira, Patrícia; Barreira, Maria; Cruz, Carla; Tomás, Joana; Luís, Ângelo; Pedro, Augusto; Queiroz, João; Sousa, FaniThe efficacy of brain therapeutics is largely hampered by the presence of the blood-brain barrier (BBB), mainly due to the failure of most (bio) pharmaceuticals to cross it. Accordingly, this study aims to develop nanocarriers for targeted delivery of recombinant precursor microRNA (pre-miR-29b), foreseeing a decrease in the expression of the BACE1 protein, with potential implications in Alzheimer's disease (AD) treatment. Stearic acid (SA) and lactoferrin (Lf) were successfully exploited as brain-targeting ligands to modify cationic polymers (chitosan (CS) or polyethyleneimine (PEI)), and its BBB penetration behavior was evaluated. The intracellular uptake of the dual-targeting drug delivery systems by neuronal cell models, as well as the gene silencing efficiency of recombinant pre-miR-29b, was analyzed in vitro. Labeled pre-miR-29b-CS/PEI-SA-Lf systems showed very strong fluorescence in the cytoplasm and nucleus of RBE4 cells, being verified the delivery of pre-miR-29b to neuronal cells after 1 h transfection. The experiment of transport across the BBB showed that CS-SA-Lf delivered 65% of recombinant pre-miR-29b in a period of 4 h, a significantly higher transport ratio than the 42% found for PEI-SA-Lf in the same time frame. Overall, a novel procedure for the dual targeting of DDS is disclosed, opening new perspectives in nanomedicines delivery, whereby a novel drug delivery system harvests the merits and properties of the different immobilized ligands.
- Smart micelleplexes as a new therapeutic approach for RNA deliveryPublication . Pereira, Patrícia; Barreira, Maria; Queiroz, João; Veiga, Francisco; Sousa, Fani; Figueiras, AnaRecent scientific discoveries have revealed the potential of using RNA molecules as therapeutic agents/targets. However, a significant key factor in the success of RNA-based therapeutics is the development of vehicles that allow their efficient delivery in the correct dose, time and location, without causing unwanted side effects. Areas covered: In this review, we provide an overview of the recent approaches proposed to overcome the chemical, biochemical and physiological barriers still present in the delivery of RNA-based therapeutics, in addition we will be discuss their use and drawbacks. This review highlights current knowledge and progress in the field of delivery of these therapeutic oligoribonucleotides, namely the use of micelleplexes as highly promising carriers. Finally, it is presented an analysis in what concerns to the ongoing challenges and future directions that have to be addressed to ensure the specificity and efficacy of RNA-based therapeutics for clinical application. Expert opinion: Micelleplexes can be prepared with different morphologies and stability depending on the block copolymer composition and structure. Besides, micelleplex functionalization with active targeting ligands and/or polymers allows RNA delivery or co-delivery (with chemotherapeutics agents) in a single nanocarrier, improving their therapeutic efficacy, selectivity and RNA release.